ClinVar Miner

Submissions for variant NM_000314.7(PTEN):c.640C>T (p.Gln214Ter) (rs121909227)

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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000491311 SCV000579982 pathogenic Inborn genetic diseases 2016-10-19 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: POSITIVE: Relevant Alteration(s) Detected
GeneDx RCV000657583 SCV000779320 pathogenic not provided 2017-10-31 criteria provided, single submitter clinical testing This pathogenic variant is denoted PTEN c.640C>T at the cDNA level and p.Gln214Ter (Q214X) at the protein level. The substitution creates a nonsense variant, which changes a Glutamine to a premature stop codon (CAG>TAG), and is predicted to cause loss of normal protein function through either protein truncation or nonsense-mediated mRNA decay. PTEN Gln214Ter has been reported in several patients with Cowden syndrome (Longy 1998, Sanson 1999, Bussaglia 2002, Tan 2011, Chen 2016), as well as in an individual with breast and other cancers but without typical features of Cowden syndrome (Tate 2007). We consider this variant to be pathogenic.
Ambry Genetics RCV001025234 SCV001187387 pathogenic Hereditary cancer-predisposing syndrome 2019-01-30 criteria provided, single submitter clinical testing Alterations resulting in premature truncation (e.g.reading frame shift, nonsense)
Invitae RCV001204841 SCV001376067 pathogenic PTEN hamartoma tumor syndrome 2019-06-07 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Gln214*) in the PTEN gene. It is expected to result in an absent or disrupted protein product. This variant is not present in population databases (ExAC no frequency). This variant has been observed in individuals with a diagnosis or suspicion of Cowden syndrome (PMID: 17954274, 10606430, 9832032, 28086757, 21659347, 23160955, 27477328) including an observed de novo occurrence in at least one individual (PMID: 9832032). ClinVar contains an entry for this variant (Variation ID: 7827). Loss-of-function variants in PTEN are known to be pathogenic (PMID: 9467011, 21194675). For these reasons, this variant has been classified as Pathogenic.
OMIM RCV000008273 SCV000028480 pathogenic Cowden syndrome 1 1998-11-01 no assertion criteria provided literature only
Department of Pediatrics and Neonatology,Nagoya City University Graduate School of Medical Sciences RCV000416592 SCV000264588 pathogenic Macrocephaly/autism syndrome 2015-11-01 no assertion criteria provided research Patient, a 4 year-old girl, showed mild developmental delay and dysmorphic facial features. Her last head circumference was 57 cm (+4.1SD). The expression level of phosphorylated S6 ribosomal protein in her lymphoblastoid cell line was elevated.

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